title: Human β-defensin 2 induces extracellular accumulation of adenosine in Escherichia coli.
abstract: Human β-defensins are host defense peptides performing antimicrobial as well as immunomodulatory functions. The present study investigated whether treatment of Escherichia coli with human β-defensin 2 could generate extracellular molecules of relevance for immune regulation. Mass spectrometry analysis of bacterial supernatants detected the accumulation of purine nucleosides triggered by β-defensin 2 treatment. Other cationic antimicrobial peptides tested presented variable outcomes with regard to extracellular adenosine accumulation; human β-defensin 2 was the most efficient at inducing this response. Structural and biochemical evidence indicated that a mechanism other than plain lysis was involved in the observed phenomenon. By use of isotope ((13)C) labeling, extracellular adenosine was found to be derived from preexistent RNA, and a direct interaction between the peptide and bacterial nucleic acid was documented for the first time for β-defensin 2. Taken together, the data suggest that defensin activity on a bacterial target may alter local levels of adenosine, a well-known immunomodulator influencing inflammatory processes.
authors.affiliation: Chemical Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany. estrela.abe@gmail.com
authors.forename: Andreia Bergamo
authors.initials: AB
authors.lastname: Estrela
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Maximiliano Gabriel
authors.initials: MG
authors.lastname: Gutierrez
authors.forename: Gabriella
authors.initials: G
authors.lastname: Molinari
authors.forename: Wolf-Rainer
authors.initials: WR
authors.lastname: Abraham
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002853:Chromatography, Liquid; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D011485:Protein Binding; D012329:RNA, Bacterial / Q000378:metabolism*; D013194:Staining and Labeling; D023083:beta-Defensins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D002250:Carbon Radioisotopes; C106641:DEFB4A protein, human; D012329:RNA, Bacterial; D023083:beta-Defensins; D000241:Adenosine